1. Field of the Invention
The present invention relates to an integrated appendage mounted, e.g., tail, pulse oximeter and blood pressure measurement apparatus for animal research.
2. Background Information
Pulse oximetry is a non invasive method that allows for the monitoring of the oxygenation of a subject's blood, generally a human or animal patient or an animal (or possibly human) research subject. The patient/research distinction is particularly important in animals where the data gathering is the primary focus, as opposed to care giving, and where the physiologic data being obtained may, necessarily, be at extreme boundaries for the animal.
As a brief history of pulse oximetry, it has been reported that in 1935 an inventor Matthes developed the first 2-wavelength earlobe O2 saturation meter with red and green filters, later switched to red and infrared filters. This was the first device to measure O2 saturation. Further in 1949 an inventor Wood added a pressure capsule to squeeze blood out of the earlobe to obtain zero setting in an effort to obtain absolute O2 saturation value when blood was readmitted. The concept is similar to today's conventional pulse oximetry but suffered due to unstable photocells and light sources and the method was not used clinically. In 1964 an inventor Shaw assembled the first absolute reading ear oximeter by using eight wavelengths of light which was commercialized by Hewlett Packard, and its use was limited to pulmonary functions due to cost and size.
Effectively, modern pulse oximetry was developed in 1972, by Aoyagi at Nihon Kohden using the ratio of red to infrared light absorption of pulsating components at the measuring site, and this design was commercialized by BIOX/Ohmeda in 1981 and Nellcor, Inc. in 1983. Prior to the introduction of these commercial pulse oximeters, a patient's oxygenation was determined by a painful arterial blood gas, a single point measure which typically took a minimum of 20-30 minutes processing by a laboratory. It is worthy to note that in the absence of oxygenation, damage to the human brain starts in 5 minutes with brain death in a human beginning in another 10-15 minutes. Prior to its introduction, studies in anesthesia journals estimated US patient mortality as a consequence of undetected hypoxemia at 2,000 to 10,000 deaths per year, with no known estimate of patient morbidity. Pulse oximetry has become a standard of care for human patients since the mid to late 1980s. Pulse oximetry has been a critical research tool for obtaining associated physiologic parameters in humans and larger animals for at least as long.
In pulse oximetry a sensor is placed on a thin part of the subject's anatomy, such as a human fingertip or earlobe, or in the case of a neonate, across a foot, and two wavelengths of light, generally red and infrared wavelengths, are passed from one side to the other. Changing absorbance of each of the two wavelengths is measured, allowing determination of the absorbances due to the pulsing arterial alone, excluding venous blood, skin, bone, muscle, fat, etc. Based upon the ratio of changing absorbance of the red and infrared light caused by the difference in color between oxygen-bound (bright red) and oxygen unbound (dark red or blue, in severe cases) blood hemoglobin, a measure of oxygenation (the per cent of hemoglobin molecules bound with oxygen molecules) can be made.
The measured signals are also utilized to determine other physical parameters of the subjects, such as heart rate (pulse rate). Starr Life Sciences, Inc. has utilized pulse oximetry measurements to calculate other physiologic parameters such as breath rate, pulse distension, and breath distention, which can be particularly useful in various research applications.
Regarding human and animal pulse oximetry, the underlying theory of operation remains the same. However, consideration must be made for the particular subject or range of subjects in the design of the pulse oximeter, for example the sensor must fit the desired subject (e.g., a medical pulse oximeter for an adult human finger simply will not adequately fit onto a mouse finger or paw; and regarding signal processing the signal areas that are merely noise in a human application can represent signals of interest in animal applications due to the subject physiology). Consequently there can be significant design considerations in developing a pulse oximeter for small mammals or for neonates or for adult humans, but, again the underlying theory of operation remains substantially the same.
Blood pressure refers to the force exerted by circulating blood on the walls of blood vessels, and constitutes one of the principal vital signs of a patient or subject (human or animal). The pressure of the circulating blood decreases as blood moves through arteries, arterioles, capillaries and veins; the term blood pressure generally refers to arterial blood pressure, i.e., the pressure in the larger arteries, arteries being the blood vessels which take blood away from the heart. Blood pressure in humans is most commonly measured via a device called a sphygmomanometer, which traditionally uses the height of a column of mercury to reflect the circulating pressure. Although many modern blood pressure devices no longer use mercury, blood pressure values are still universally reported in millimeters of mercury.
Systolic pressure is defined as the peak pressure in the arteries, which occurs near the beginning of the cardiac cycle; the diastolic pressure is the lowest pressure (at the resting phase of the cardiac cycle). The average pressure throughout the cardiac cycle is reported as mean arterial pressure; the pulse pressure reflects the difference between the maximum and minimum pressures means.
The ability to accurately and non invasively measure the systolic and diastolic blood pressure, in addition to other blood flow parameters in rodents, and other animals, is of great clinical value to the animal researcher. The general non-invasive blood pressure methodology for measuring blood pressure in rodents comprises utilizing a tail cuff placed proximally on the tail to occlude the blood flow. The subject's tail is threaded through the tail cuff. Upon deflation, one of several types of non invasive blood pressure sensors, placed distal to the occlusion cuff, will attempt to measure the blood pressure. There are several types of non invasive blood pressure sensor technologies: including photoplethysmography, piezoplethysmography, and volume pressure recording. Each of these methods will utilize an occlusion tail-cuff as part of the methodology.
It is worthwhile to note that direct blood pressure measurement in research applications is an invasive surgical procedure with the expense and time involved with invasive procedures, but this invasive procedure is often considered as a more precise measurement and this is used to compare the accuracy of non-invasive blood pressure technologies. Direct blood pressure should be performed on the rodent's carotid artery, rather than the femoral artery.
Photoplethysmography based blood pressure measurements in rodents is the first and oldest sensor type and is a light-based technology, photoplethysmography (PPG) described above in general. The aim is to record the first appearance of the pulse when it re-enters the tail artery during the deflation cycle of the proximal occlusion cuff. Photoplethysmography blood pressure measurement utilizes a standard light source or a LED light source to record the pulse signal wave. As such, this light-based plethysmographic method uses the light source to illuminate a small spot on the tail and attempts to record the pulse.
A second non invasive blood pressure sensor technology is piezoplethysmography. Piezoplethysmography and photoplethysmography both require the same first appearance of pulse in the tail to record the systolic blood pressure and heart rate. Whereas photoplethysmography uses a light source to record the pulse signal, piezoplethysmography utilizes piezoelectric ceramic crystals to record blood pressure readings. From a technical point of view, piezoplethysmography acquires blood pressure readings when the re-appearance of the pulse in the rodent's tail produces a change that can be equated to a voltage shift. The voltage shift momentarily deforms the ceramic crystals and the change is converted to millimeters of mercury for blood pressure readings.
A third sensor technology is volume pressure recording that utilizes a differential pressure transducer to non-invasively measure the blood volume in the tail of a subject.
Representative, commercial rodent tail cuff blood pressure monitoring devices are available from IITC, Life Science, Inc.; Columbus Instruments, Inc.; and Kent Scientific.
Non-invasive tail mounted blood pressure measurement systems for animals should be designed to comfortably warm the animal, reduce the animal's stress and enhance blood flow to the tail. The rodent's core body temperature is very important for accurate and consistent blood pressure measurements. The animal must have adequate blood flow in the tail to acquire a blood pressure signal. Thermo-regulation is the method by which the animal reduces its core body temperature, dissipates heat through its tail and generates tail blood flow. Anesthetized animals may have a lower body temperature than awake animals so additional care must be administered to maintain the animal's proper core body temperature.
An infrared warming blanket or a re-circulating water pump with a warm water blanket are conventional methods to maintain the animal's proper core body temperature. The animal should preferably be warm and comfortable but never hot. Extreme care must be exercised to never overheat the animal. Hot air heating chambers, heat lamps, heating platforms that apply direct heat to the animal's feet have been suggested as well as tail cuff heating devices. However care must be taken with any thermal regulation system to avoid overheating the animal that may increase the animal's respiratory rate, thereby increasing the animal's stress level. These conditions can elicit poor thermo-regulatory responses and may create inconsistent and inaccurate blood pressure readings.
The above discussion notes that blood pressure monitoring in small mammals is somewhat well developed and a very useful tool for researchers. The tail based measurements still provides unique problems for measuring physiologic measurements in rodents. Further, pulse oximetry has been expanded to be effectively applied to small mammals, such as mice as shown in the MouseOx® brand small mammal pulse oximeter available from the assignee, and has provided further useful tools to researchers. There remains a need in the art to effectively expand the useful tools applicable to researchers, to simplify there use and improve the physiologic results.